In consortium with researchers at Washington University School of Medicine, the University of Connecticut Health Center, the University of North Carolina School of Medicine, and the University of Florida, we propose to create a highly integrated Center for Cancer Physics at Johns Hopkins University. Our integrated approach will allow a systematic analysis and quantitative understanding of how various mechanical stimuli - cell-cell adhesive forces, compressional forces, interstitial fluid flow causing shear stresses and hydrostatic pressure, adhesive forces between cell and substrate, cell-mediated traction and protrusive forces within the matrix, steric forces during extravasation and intravasation, shear forces in the circulatory system - modulate angiogenesis, cell dissociation from the primary tumor, three-dimensional motility in the matrix, basement membrane and vascular invasion, tumor cell-host cell interactions in the circulatory system, and cell proliferation at the secondary tumor site. To address the complexity of the role of forces in cancer, we have developed three interrelated projects. To overcome the lack of predictive computational models of cancer, computational and experimental biophysicists as well as cancer biologists will work together in the Center to systematically develop a quantitative understanding of forces in the metastatic cascade. To overcome the lack of consistency in the use of models and biophysical methods, the projects will use the same biophysical methods and the same cancer cell lines. To overcome language and cultural barriers between cancer biologists and physicists/engineers, the Center will establish a comprehensive predoctoral and postdoctoral multidisciplinary training program. Johns Hopkins University cancer biologists, engineers, and physicists in the Center will work in the same laboratories.